GZMB

granzyme B, the group of Granule associated serine proteases of immune defence

Basic information

Region (hg38): 14:24630953-24634267

Previous symbols: [ "CTLA1", "CSPB" ]

Links

ENSG00000100453 ∙ NCBI:3002 ∙ OMIM:123910 ∙ HGNC:4709 ∙ Uniprot:P10144 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GZMB gene.

• Inborn genetic diseases (14 variants)
• not provided (8 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GZMB gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	2	4
missense			15	1	1	17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	15	3	4

Variants in GZMB

This is a list of pathogenic ClinVar variants found in the GZMB region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-24631075-T-C		not specified	Uncertain significance (May 18, 2023)
14-24631079-G-A		not specified	Uncertain significance (Dec 06, 2022)
14-24631084-A-G		not specified	Uncertain significance (Dec 15, 2023)
14-24631084-A-T		not specified	Uncertain significance (Aug 09, 2021)
14-24631111-C-A		not specified	Uncertain significance (Feb 16, 2023)
14-24631153-C-T		not specified	Uncertain significance (Sep 14, 2023)
14-24631158-A-G			Benign (Aug 10, 2018)
14-24631185-G-T			Likely benign (May 02, 2018)
14-24631919-T-C			Uncertain significance (Feb 01, 2023)
14-24631959-C-T		not specified	Uncertain significance (Aug 22, 2023)
14-24631965-T-C		not specified	Uncertain significance (Apr 13, 2022)
14-24631978-T-C			Likely benign (Jun 06, 2018)
14-24632022-C-T		not specified	Uncertain significance (Mar 31, 2023)
14-24632075-C-T		not specified	Uncertain significance (May 11, 2022)
14-24632342-G-A			Likely benign (Jul 25, 2017)
14-24632383-G-C			Benign (Jul 25, 2017)
14-24632423-T-C			Benign (Jul 25, 2017)
14-24632449-C-T		not specified	Uncertain significance (Sep 27, 2022)
14-24632943-C-T		not specified	Uncertain significance (Nov 17, 2023)
14-24632967-C-T		not specified	Uncertain significance (Jul 06, 2021)
14-24632975-C-T		not specified	Uncertain significance (Mar 27, 2023)
14-24633024-G-A		not specified	Uncertain significance (Aug 02, 2021)
14-24633048-C-T		not specified	Uncertain significance (Sep 22, 2022)
14-24633051-C-T		not specified	Uncertain significance (May 24, 2023)
14-24634096-G-C			Benign (Jun 08, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GZMB	protein_coding	protein_coding	ENST00000216341	5	3314

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.67e-14	0.00165	125704	0	43	125747	0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.306	153	143	1.07	0.00000779	1605
Missense in Polyphen		49	44.552	1.0998		503
Synonymous	-1.24	67	55.3	1.21	0.00000324	482
Loss of Function	-1.71	17	10.9	1.56	5.42e-7	113

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000301	0.000301
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000196	0.000193
Middle Eastern	0.000163	0.000163
South Asian	0.000229	0.000229
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: This enzyme is necessary for target cell lysis in cell- mediated immune responses. It cleaves after Asp. Seems to be linked to an activation cascade of caspases (aspartate-specific cysteine proteases) responsible for apoptosis execution. Cleaves caspase-3, -7, -9 and 10 to give rise to active enzymes mediating apoptosis.
• Pathway: Type I diabetes mellitus - Homo sapiens (human);Allograft rejection - Homo sapiens (human);Graft-versus-host disease - Homo sapiens (human);Autoimmune thyroid disease - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Apoptosis - Homo sapiens (human);Signaling by NOTCH2;Allograft Rejection;Apoptosis;Apoptotic Signaling Pathway;Hematopoietic Stem Cell Gene Regulation by GABP alpha-beta Complex;Oxidative phosphorylation;Signal Transduction;caspase cascade in apoptosis;granzyme a mediated apoptosis pathway;apoptotic dna-fragmentation and tissue homeostasis;DroToll-like;Intrinsic Pathway for Apoptosis;Apoptosis;Programmed Cell Death;NOTCH2 intracellular domain regulates transcription;Signaling by NOTCH2;Signaling by NOTCH;Activation, myristolyation of BID and translocation to mitochondria;Caspase Cascade in Apoptosis;Downstream signaling in naïve CD8+ T cells;IL12-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.526

Intolerance Scores

• loftool: 0.415
• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.23

Haploinsufficiency Scores

• pHI: 0.0475
• hipred: N
• hipred_score: 0.252
• ghis: 0.386

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.501

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gzme

Gene ontology

• Biological process: proteolysis;apoptotic process;granzyme-mediated apoptotic signaling pathway;cytolysis;natural killer cell mediated cytotoxicity;positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
• Cellular component: immunological synapse;nucleus;cytoplasm;mitochondrion;cytosol;membrane;secretory granule
• Molecular function: serine-type endopeptidase activity;protein binding;serine-type peptidase activity